Obese (ob/ob) mice and rats with VMH-lesions become obese even if pair-fed to their respective controls. These animals must therefore expend less energy than normal. Our overall goal is to identify mechanisms responsible for the increased efficiency of dietary energy retention in obese animals and to understand how regulation of these processes is altered. Our working hypothesis is that low Na+, K+ ATPase in skeletal muscle and low heat output by brown adipose tissue contribute to the high retention of dietary energy, with the major thrust of the porposed studies on the latter process. Effects of diet composition and environmental temperature on sympathetic nervous system activity, as indicated by norepinephrine turnover, in brown adipose tissue and selected other organs of lean and obese animals will be examined. Because thermogenin appears to be the unique protein in brown adipose tissue that permits high heat production upon sympathetic stimulation we will also assay the availability of this protein in brown adipose tissue mitochondria by the -3H-GDP binding procedure. The role of adrenal corticosterone and adrenal catecholamines in induction of hyperphagia, in control of Na+, K+ ATPase in skeletal muscle and in brown adipose tissue metabolism in obese mice and rats will be evaluated. Comparisons of obese (ob/ob) mice and rats with hypothalamic lesions should help identify key metabolic events that permit high retention of dietary energy in these animals. These data should increase our understanding of the metabolic basis for development of obesity and should aid us in developing improved nutritional approaches to cope with the prevention and control of obesity.
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